It is proposed that the intracellular concentration of Ca 2 ion in the human erythrocyte is determined by means of a regulatory process that involves coordinate and/or sequential modulation by both Ca 2 ion and adenosine 3':5'-monophosphate (cAMP). We have evidence that suggests that the participation of cAMP entails protein phosphorylation as catalyzed by a cAMP-dependent protein kinase.